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Laboratory / Animal / Preclinical Studies

    continued...

    In another study, Reviewed in [11] intratumoral injection of NDV strain Ulster into growing ESb tumors in immunocompetent mice led to a cessation of tumor growth and an absence of metastases in 42% of treated animals. In the remaining mice, tumor growth and metastatic spread continued at the same rate as in control animals. Reviewed in [11] Additional results from this study indicated that the anticancer effect in the responding animals was due primarily to the activation of T cells directed against a tumor-specific antigen on ESb cells rather than a virus antigen. Reviewed in [11]

    Other studies with NDV Ulster and the ESb tumor model support the idea that virus proteins inserted in the plasma membrane of NDV-infected cancer cells may help the immune system recognize tumor-specific antigens better, potentially leading to an increased ability to kill uninfected cancer cells and virus-infected cells.[25,28,31,36,37,39] Reviewed in [11,20,43,45,46] At least four studies [25,28,37,39] Reviewed in [45,46] have shown that T cells isolated from mice that have growing ESb tumors can be activated in vitro by co-culture with NDV-infected ESb cells and that the resulting activated T cells possess an enhanced ability to kill uninfected ESb cells in vitro. In addition, two in vivo studies [31] Reviewed in [11] have shown that mice injected with NDV-infected, irradiated ESb cells are 30 to 250 times more resistant to later injection with proliferating ESb cells than mice that are initially injected with uninfected, irradiated ESb cells. Furthermore, at least two in vivo studies have demonstrated that vaccination of mice with NDV-infected, irradiated ESb cells after surgery to remove a growing ESb primary tumor can prevent the growth of metastatic tumors in approximately 50% of treated animals.[31,36] Reviewed in [11,43,45,46] When the surviving mice were subsequently injected with proliferating ESb cells, they all remained free of cancer, indicating that the NDV/tumor cell vaccine had conferred anticancer immunity.[31,36] Reviewed in [11,45,46] Similar results were obtained from in vivo studies that employed the mouse B16 melanoma model,[33] the mouse Lewis lung carcinoma model,[32] or the guinea pig L10 hepatocellular carcinoma model.[34]

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